DE19644343A1 - Taste-neutral microcapsules, process for their preparation and their use - Google Patents

Abstract

The invention relates to neutral tasting microcapsules, the method for their manufacturing and their use as human or animal food additives and as carrier systems for medicaments. In accordance with the invention, said capsules consist of oligo and/or polysaccharides, for instance, alginates, which are normally indigestible in the digestive tract combined with digestible components. Preferred are substances which have an unpleasant taste on their own, for example, cod liver oil and/or linseed oil, including also their combination with other substances, e. g. mineral substances, trace elements or substances having an immunological or pharmacological effect. Said microcapsules can be used as valuable human or animal food additives and as vaccines or medicaments since the components are released in the digestive tract.

Description

The invention relates to taste-neutral microcapsules, Ver drive to their manufacture as well as their use as life or Feed additives and as pharmaceuticals.

Reduction and oxidation take place equally in the organism. The pathophysiological importance of chronic redox Dysbalances are increasingly recognized in medicine because from this new differential diagnostic and therapeutic Have consequences. In metabolism and in cellular respiration create highly reactive, short-lived oxygen radicals. Meeting fen these to neutral molecules, e.g. B. polyunsaturated fat acids, become new fatty acid radicals in a chain reaction educated. The higher the proportion in the food, the more they become more mature against peroxidation processes, if not adequate antioxidant systems protect these fatty acids. So z. B. per gram of linolenic acid in food as protection 0.6 mg vitamin E required.

Free radicals are essential. They act immunoregulatory rend. You will u. a. of macrophages and certain lympho Cyte populations synthesized to pathogens and / or to eliminate diseased cells. Radical balance too low dung consequently means reduced defense performance in their Often follow chronic inflammation and autoimmune diseases can arise.

Radical formation too strong or radical inactivation too low Over a long period of time it is just as destructive as too little Radical formation. Vulnerabilities for oxidative attacks are polyunsaturated membrane phospholipid fatty acids, carbons hydrates and DNA.

Trace elements such as zinc, manganese, selenium and copper are included for example for the function of the radical trap system Super  oxide dismutase essential, while vitamins E, C and β- Carotene itself act as a radical scavenger.

Improper nutrition, such as B. eating one too phytinrei Chen food, leads to reduced traces via metal binding absorption of elements and damage to the immune system. The change dietary habits over the past few decades resulted in a variety of antioxidant effects Plant ingredients can no longer be absorbed. Not correct understood health awareness, biological activity the food is often reduced to the purely caloric value graces, leads to extreme diets in our day, which create deficits in antioxidants. Is malnutrition the main cause of oxidative stress. Furthermore leads to life in industrialized society an increasing exposure to xenobiotics that are inhaled, percutaneously or intestinally (Household chemicals, cosmetics, insulation materials, preservatives chemicals, car exhaust, industrial pollution u. a.). Majority They have a pro-oxidative effect, so they are immunosuppressive and begin especially chronic diseases.

Due to increasing health awareness, the An enrichment of beverages with calcium a greater acceptance found. Calcium deficiency or lack of biover Availability supported bone growth disorders in ju or the formation of osteoporosis. There is a direct correlation in certain age groups between Calcium intake and bone mass. Milk is more physiological the crucial source of calcium for adolescents. With As we age, milk consumption is reduced so that an undersupply of calcium often at an early stage point occurs.

In adults, this leads to progressive deminerali bone fixation. In addition to the supply of calcium, Re sorption and bioavailability Vitamin D is vital. Last but not least Calcium absorption is also regulated hormonally. Lacking Calcium supply, an undersupply of vitamin D and the  normal hormonal regulation cause that in particular Women over the age of 40 are at risk of osteoporosis.

Calcium is also an essential blood coagulation factor and indispensable for the conduction of excitation in nerves and mus keln. The calcium requirement depends on age, gender and performance.

So z. B. the enrichment of drinks with calcium salts is the subject of several patents (EP-A 0 244 903, EP-A 0 350 523, EP-A 0 227 174). They include the addition of calci connections in various forms to fruit juices Beverages.

Furthermore, for. B. vegetable oils or fish oils such. B. liver tran also valuable substances, which among other things characterized by a high content of vitamins A and D. So is known, among other things, that the intake of milk products nissen (milk contains 0.12% calcium), which ver sets, significantly the absorption of calcium from the Milk increases. The intense, mostly uncomfortable Own taste, however, leads to widespread rejection nung.

Also the addition of other vegetable oils or fish oils that are particularly rich in omega-3 fatty acids, to foods in connection with other natural "radical scavengers", could make a vital contribution to healthy eating be.

The aim of the invention is therefore from nutritional physiology desirable combinations with substances to re-sit, which so far from physical and / or chemi interactions or with current traffic conceptions inconsistent or for sensory reasons were not possible, and due to the deficits in the diet can be reduced or reduced.

It was therefore the object of the invention, nutritionally physiologically important substances, such as. B. minerals,  Trace elements, vegetable, fish oils and / or others, their Its own taste is generally perceived as unpleasant is, possibly also immunological and pharmacological active ingredient fe to be formulated so that it can be used in other Means are suitable without the end product being negative sensory to influence, are stable in the aqueous environment and after Auf can only be released in the small intestine.

The task is inventively by taste neutral microcapsules dissolved, such substances close that usually as having an uncomfortable own taste may be felt in combination with each other and / or with other substances. Substances in the sin The invention is also immunological or pharmacological active ingredients. Surprisingly, microcapsules were ready to be put out in the digestive tract per se, indigestible union oligosaccharides and / or polysaccharides exist in Kombinati on with digestible components in the capsule wall, whereby the digestible components up to a proportion Make up 80%. As indigestible compounds Al gic acid, polymers of alginic acid, alginates, pectins and / or Xanthans used.

It is preferably alginic acid or alginates which with a physiologically tolerable metal salt, e.g. B. one Calcium salt, combined can be used. For the encapsulation alginic acid (E 400) and its salts are particularly suitable (E 401-E 404). Because alginates are not digestible enough Untracked are unlocked by the fiction appropriate installation of digestible components in the capsule wall the release of the encapsulated ingredients in the digestive system reached without traction. It was surprising that this additional components the size distribution and stability of the Do not negatively influence and change microcapsules.

Alginates are already used in the food industry lung (WO 91/19424). Alginic acid and its salts are in the Food industry approved substances. You can do it all Foods including weaning foods for infants  and small children in the necessary for the technological process appropriate dimensions are added.

The fat substitutes known from WO-A-91/19424 under Ver The use of emulsified oils and and alginates mediate Mouthfeel as it is and will be caused by fat used for the production of calorie-reduced food. They do not dissolve and are completely removed again divorced.

The inventive insertion of digestible Be constituents in the capsule wall, however, it is possible that the digestive enzymes holes appear in the capsules and the Ingredients can be released.

It is therefore possible to combine those fabrics that conventional due to negative sensory influence or insufficient miscibility not included in the diet could be set.

In contrast to enteric-coated encapsulations that come from conventionally used for the administration of drugs are, the microcapsules according to the invention dissolve in aq milieu with a pH value above that of gastric juice alone on. They are only digested by digestive enzymes such. B. pancreatic amylases, which act in the small intestine solved.

The digestible components are in the microcapsules preferably mono-, oligo- and / or polysaccharides, (poly) hydroxy carboxylic acids, fatty acids and their salts and Derivatives and amino acids, their salts and their derivatives, included, such as B. gluconic acid, gluconates, lactic acid, lac tate, starch or starch derivatives, preferably starch, modes starch or lactate.

Preferred ingredients according to the invention are plant and / or Fish oils such as B. linseed oil, cod liver oil, borage oil, and / or minerals, trace elements, such as. B. Connections of selenium, zinc, copper, manganese, iron and high protein Fabrics such as B. Spirulina in combination with calcium containing connections. Cod liver oil is particularly preferred,  if necessary with linseed oil, also in combination with trace elements and / or other substances included. Furthermore the microcapsules according to the invention are suitable for administration Submission of vaccines and drugs that are only thin intestines are supposed to be effective.

The invention also relates to a method for the manufacture position of the microcapsules according to the invention and their Ver application as food or feed additives as well as Carrier system for vaccines or pharmaceuticals.

The microcapsules are made by digesting the indigestible Lichen oligosaccharides and / or polysaccharides together with digestible Chen components dissolves and using known Ultra sound synthesis one after the other or simultaneously closing substances and possibly a Ca-containing Solution dosed. The microcapsules formed are through Filtration separated and then with cross-flow Filtration further cleaned and resuspended. You point surprisingly a typical size distribution between 0.5 µm and 20 µm.

The microcapsules so produced are according to the invention further as additives in food or feed or as a vehicle for vaccines and drugs puts.

The microcapsules according to the invention are in the desired ones Ratios of quantities during or after their manufacture in a carrier food or feed is added. Preferably food is produced with the addition of Alginate-encapsulated oils or aqueous solutions and / or Dispersions. According to the thermal sensitivity of the Le Food ingredients can be preserved by chemi preservatives, filtration and aseptic filling treatment, pasteurization or autoclaving. The free setting of the encapsulated food or additives in the The digestive system is not affected. By increasing the viscosity and / or the specific weight of rivers liquids such as fruit and vegetable juices or lemonades and the like  Liquids can float or sediment animals can be prevented. The proportions are usual Chosen so that appearance and sensory properties through the addition of encapsulated foods and additives Substances are not changed or only slightly changed.

Thus, nutritional parameters can be positive changes, regulates and on the other hand also deficiency symptoms be balanced. On the one hand, by adding calcium an antioxidant stress prevention instead, on the other hand especially prevent osteoporosis.

By adding encapsulated cod liver oil to z. B. milk product Calcium absorption is also significantly increased device.

Furthermore, by z. B. encapsulated trace elements too Mineral metabolic disorders can be remedied.

Then the invention is based on exemplary embodiments ago explained.

example 1 Manufacture of encapsulated fats and oils Example 1.1 Manufacture of alginate-encapsulated fats and oils

1 g of sodium alginate is dissolved in 300 ml of water. This will under the influence of ultrasound (immersion probe: 24 kHz / 120 W / pulse operation 7: 1 per second) 30 ml of a plant or Fish oil, e.g. B. cod liver oil. After 10 min, a Lö solution of 0.4 g calcium chloride dihydrate in 10 ml water added dropwise to the same conditions. The structures Microencapsulations are separated by filtration, further cleaned by cross-flow filtration and after resus- Pension stored in 100 ml of water. The microver formed Encapsulations typically have size distributions between 0.5 µm and 20 µm.  

The sodium alginate is proportionately up to 80% by alginic acid or other soluble alginates, gluconic acid or gluconates, Fatty acids, as well as their salts and derivatives, lactic acid or Lactates, starch or starch derivatives replaced without this the size distribution of the microencapsulation changes significantly is changed. These encapsulation modifications increased the bioavailability of the encapsulated oil because in particular pancreatic enzymes efficiently lysie the built-in substances ren.

Example 1.2 Production of encapsulated cod liver oil

0.3 g sodium alginate and 0.7 g wheat starch are mixed in 300 ml Water dissolved. This is done under the influence of ultrasound (Immersion probe: 24 kHz / 120 W / pulse operation 7: 1 per second) 30 ml cod liver oil dosed. After 10 min, a solution of 0.2 g Calcium chloride dihydrate in 10 ml water under the same Conditions added dropwise. The formed micro encapsulations are separated by filtration through Cross-flow filtration further cleaned and after resuspension stored in 100 ml of water. The microencapsulations formed typically have size distributions between 0.5 µm and 20 µm.

Example 1.3

4 g of alginate are dissolved in 660 ml of water at 50 ° C. with stirring. 4 g of starch are briefly boiled up in 660 ml with stirring. Both solutions are combined with stirring. Using an Ultra-Turrax (16,000 rpm ^-1) are dispersed 250 ml cod liver oil for 10 min. About 50 ml of CaCl ₂ × 2H ₂ O (1.4 g / 100 ml) are added dropwise to this dispersion until the mass becomes highly viscous. The cleaning is done by cross-flow filtration. The capsule diameter is approximately 1 µm.

Example 2 Production of a fruit-containing drink with additives of encapsulated cod liver oil, calcium and selenium yeast

100 g sodium lactate (E 325), in the form of a 50% aqueous solution Solution, together with 10 g of selenium yeast (corresponds to 10 mg Selenium) dispersed in 1 l cod liver oil with vigorous stirring. According to the invention, this dispersion is prepared using 30 g of alginate and the equivalent amount of calcium chloride dihydrate encapsulated. The few µm capsules are made by Cross-flow filtration freed of oil residues and in Water stored.

25 g of encapsulated cod liver oil calcium lactate selenium yeast Mixtures are produced every liter by known methods added fruit juice drink added.

To increase the viscosity, fruit juices, fruit juice drinks, nectar, lemonades, showers and other drinks soak z. B. 0.5% pectin or other suitable substances added be set. After homogenization and short-time heating, NEN beverages are filled in a known manner.

The beverages thus produced according to the invention show none sensory deviation compared to those without additive of encapsulated cod liver oil-calcium lactate-selenium yeast mixture.

The consumption of 0.25 l of such a drink covers approximately 100% of the calcium, vitamin D and selenium requirement of an Er growing.

Example 3 Production of a milk product (yogurt) with the addition of encapsulated cod liver oil, calcium, spirulina and selenium yeast

80 g sodium lactate (E 325), in the form of a 50% aqueous solution Solution, together with 200 g of spirulina and 10 g of selenium yeast (corresponds to 10 mg selenium) in 1 l cod liver oil under vigorous Dispersed stirring. According to the invention, this dispersion is un ter using 30 g alginate and the equivalent amount  Encapsulated calcium chloride dihydrate. The few µm cap are made by means of cross-flow filtration of adhering oil residues freed and stored in water.

25 g of encapsulated cod liver oil calcium lactate spirulina Selenium yeast mix is added to every liter of milk mix and by known methods with the addition of suitable Bak series cultures processed into yoghurt.

The milk products thus produced according to the invention show no sensory deviation compared to those without Zu encapsulated cod liver oil calcium lactate selenium yeast Mixture.

Cover the intake of 0.25 l of such a milk product an adult's calcium and vitamin D requirements.

Example 4 Production of a boiled sausage (Bockwurst) with the addition of ver encapsulated cod liver oil, linseed oil, calcium and selenium yeast

100 g sodium lactate (E 325), in the form of a 50% aqueous solution Solution, together with 10 g of selenium yeast (corresponds to 10 mg Selenium) in 0.5 l cod liver oil and 0.5 l linseed oil (contains about 30% Omega-3 fatty acids) dispersed with vigorous stirring. This Dispersion is inventively using 30 g Al ginate and the equivalent amount of calcium chloride dihydrate ver encapsulates. The few µm capsules are Flow filtration freed of adhering oil residues and in what water stored.

50 g of the encapsulated cod liver oil linseed oil calcium lactate Selenium yeast mix with every kilogram of meat emulsion Bulk water added. After fine cutting the Sausage mass filled in artificial or natural casings and hot and rough chert.

The scalded sausages so produced according to the invention show none sensory deviation compared to those without additive of encapsulated cod liver oil, linseed oil, calcium lactate, selenium yeast Mixture.  

Consuming a Bockwurst (100 g) covers about 50% of the Calcium, selenium and vitamin D requirements. One according to the invention Bockwurst produced in this way contains about 500 mg of omega-3 Fatty acids, which together with selenium have an important function inactivating free radicals.

Example 5 Production of a delicatessen product with the addition of ver encapsulated cod liver oil, spirulina, calcium and selenium yeast

80 g sodium lactate (E 325), in the form of a 50% aqueous solution Solution, together with 10 g of selenium yeast (corresponds to 10 mg Selenium) and 200 g spirulina in 1 l cod liver oil and vigorously dispersed while stirring. This dispersion is according to the invention using 30 g alginate and the equivalent amount Encapsulated calcium chloride dihydrate. The few µm cap are made by means of cross-flow filtration of adhering oil residues freed and stored in water.

100 g of encapsulated cod liver oil spirulina calcium lactate Selenium yeast mixture is homogenized with 900 g mayonnaise.

This basic mayonnaise serves as the basis for the production of delicatessen products with the addition of meat, Meat, fish, mussels, crayfish, vegetables, fruit, boiled egg and other ingredients in different weight percentages len.

The delicatessen products thus produced according to the invention no sensory deviation compared to those without Adding encapsulated cod liver oil spirulina calcium lactate Selenium yeast mixture.

Example 6 Production of an orally administrable vaccine against the Transmissible gastroenteritis (TGE) in pigs

The causative agent of TGE is an acid-labile corona virus. The he the piglet becomes ill within the first 10 days of life  100% morbidity. Mortality is around 90%. The Piglets can be protected relatively well via colostral Antibodies from breast milk. Crucial for protection are sIgA. Their synthesis is largely via the gut asso ornamental controlled lymphatic system. So the vaccine must administered orally. To prevent virus inactivity tion in the stomach was encapsulated according to the invention.

About 10 ^8.5 culture-infectious doses (KID) _{50 of} an apathogenic TGE virus strain are dried by lyophilization. The lyophilisate is dispersed in 250 ml of cod liver oil immediately before the encapsulation. 4 g of alginate are dissolved in 660 ml of water at 50 ° C with stirring, 4 g of starch are briefly boiled in 660 ml with stirring. Both solutions are combined with stirring. Using an Ultra-Turrax (16,000 rpm ^-1) alternates the cod liver oil 250 ml virus suspension for 10 min disper. About 50 ml of CaCl ₂ × 2H ₂ O (1.4 g / 100 ml) are added dropwise to this dispersion until the mass is highly viscous. The cleaning is done by cross-flow filtration. The capsule diameter is approximately 1 µm. After the capsules have dissolved, the virus content in the capsule can be titrated.

8 pregnant sows were given 10 ^6.5 KID ₅₀ in the encapsulated form according to the invention orally together with liquid feed (about 5 g microcapsules) on 7 consecutive days 4-5 weeks ante partum (ap). A second immunization phase was carried out on 3 consecutive days for 14 days ap as described above. All animals tolerated the immunization without reaction.

The 54 piglets from the 8 litters were orally infected with 10 ⁵ KID _{50 of} a virulent TGE virus rock strain within the first 12 hours of life. Infected 40 piglets from 5 litters of unimmunized mother sows were also used as controls.

The following results were achieved:

As a result of the immunization, the sows transmit a spe specific passive protection with the colostrum on their offspring men.

Example 7 Release of barbital after capsule digestion with amylase

8 g of barbital are dispersed in 250 ml of cod liver oil using Ultra-Turrax. 4 g of alginate are dissolved in 660 ml of water at 50 ° C. with stirring. 4 g of starch are briefly boiled in 660 ml with stirring. Both solutions are added together with stirring. Using an Ultra-Turrax (16,000 rpm ^-1) is the 250 ml cod liver oil barbital suspension dispersed for 10 min. About 50 ml CaCl ₂ × 2H ₂ O (1.4 g / 100 ml) are added dropwise to this dispersion until the mass is highly viscous. The cleaning is carried out by cross-flow filtration. The capsule diameter is about 1 µm. A 10% suspension is prepared in isotonic buffer. Microcapsules with the same content served as a control for the release experiment, but were produced without the addition of starch but only with alginate. 1 ml each of the suspension was incubated with 500 units of amylase at 37 ° C. for 4 h. Incubation without amylase was carried out in parallel with 1 ml each. The detection of released barbital was carried out according to DAB using thin-layer chromatography. Since the capsules do not dissolve in the superplasticizer, the suspension can be used to detect the barbital released without first separating the capsules.

From the digested alginate starch capsules according to the invention about 1 mg barbital per ml microcapsule was released. The corresponds to about 30-50% of the encapsulated amount of barbital. Out The conventional alginate capsules did not produce any barbital amounts released, which can be determined with this detection method are.

Claims (16)

1. Taste-neutral microcapsules from in the digestive tract per se indigestible oligosaccharides and / or polysaccharides, in which one or more substances are included are and the additional digestible components in the Capsule wall included. 2. Microcapsules according to claim 1, characterized in that the indigestible oligosaccharides and / or polysaccharides Alginic acid, polymers of alginic acid, alginates, pectins and / or xanthans are physiological along with one tolerable metal salt, such as. B. a calcium salt. 3. Microcapsules according to claim 1 or 2, characterized records that as digestible components with a Ratio up to 80% mono, oligo and / or butt lysaccharides, (poly) hydroxycarboxylic acids, fatty acids so such as their salts and derivatives and amino acids whose Salts and their derivatives are included. 4. Microcapsules according to claim 3, characterized in that that the digestible components are gluconic acid, glucona te, lactic acid, lactates, starch and / or starch derivatives are. 5. Microcapsules according to claim 4, characterized in that the digestible components modified starch Starch or lactate. 6. Microcapsules according to one of claims 1 to 5, characterized characterized that food or groceries Substitutes are included, usually because of negative sensory influence on the end product or not with the current traffic perceptions agree or because of physical and / or che mixer interactions are not used. 7. Microcapsules according to one of claims 1 to 6, characterized characterized in that as substances vegetable, fish oils and / or trace elements are included.   8. Microcapsules according to one of claims 1 to 7, characterized characterized in that both apolar and polar liquid on their own or as a solubilizer or dispersion mediator are included. 9. Microcapsules according to claim 8, characterized in that as apolar solution or dispersion mediator Le bertran or oils with a high content of unsaturated Fatty acids are used. 10. Microcapsules according to one of claims 1 to 9, characterized characterized in that the indigestible polysaccharide Al ginic acid or an alginate, which is one or more Includes substances that make you uncomfortable which have their own taste, in combination with a Calcium-containing compound and that in the capsule wall as a digestible ingredient, starch, modified starch ke or lactate is included. 11. Microcapsules according to one of claims 1 to 10, characterized characterized in that substances with immunological or pharmacological effects are included. 12. Process for the production of taste-neutral micro Capsules of claims 1 to 11, characterized in that that they are made by ultrasound synthesis, by Cross-flow filtration cleaned and then resus be oscillated, whereby a narrow size distribution of the Microencapsulation is achieved. 13. Use of microcapsules of claims 1 to 10 since characterized by that they are sewing for change physiological parameters for each substance preferably to a food during or after Her position can be added without the sensory properties of the end product. 14. Use of the microcapsules according to claim 13 for vorbeu of mineral metabolism disorders or against oxida tive stress.   15. Use of microcapsules according to claims 1 to 11 as vaccines or medicines for intestinal release bypassing the disruption in the stomach. 16. Use of microcapsules of claims 1 to 10 since characterized by that they are sewing for change physiological parameters of feed during or added after manufacture without the senso sustainable properties of the end product influence.